Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2017 Oct;40(10):1087-1095.
doi: 10.1111/pace.13166. Epub 2017 Sep 15.

Roles of impaired intracellular calcium cycling in arrhythmogenicity of diabetic mouse model

Chung-Chuan Chou  1   2 , Chien-Te Ho  1 , Hui-Ling Lee  3 , Yen Chu  2   4 , Tzung-Hai Yen  2   5 , Ming-Shien Wen  1   2 , Shien-Fong Lin  6 , Cheng-Hung Lee  1   2 , Po-Cheng Chang  1   2
Affiliations

Roles of impaired intracellular calcium cycling in arrhythmogenicity of diabetic mouse model

Chung-Chuan Chou et al. Pacing Clin Electrophysiol. 2017 Oct.

Abstract

Background: Diabetes mellitus is associated an increased risk of ventricular arrhythmias (VAs), but the underlying electrophysiological mechanisms are not fully explored. This study was aimed to test whether dynamic factors and Cai handling play roles in arrhythmogenesis of a diabetic animal model.

Methods: We used 26 db/db type 2 diabetes mice and 28 control mice in this study. VA inducibility was evaluated in vivo under isoflurane general anesthesia. The intracellular Ca2+ (Cai ) and membrane voltage (Vm ) signals of the Langendorff-perfused mouse hearts were simultaneously recorded using the optical mapping technique. Action potential duration (APD), Cai dynamics conduction velocity (CV), and arrhythmogenic alternans were analyzed. Western blot was conducted to examine expressions of calcium handling and associated ion channels proteins.

Results: The diabetic db/db mice showed significantly increased VA inducibility and severity. Longer APD and Cai transient duration and slower Cai decay and CV in the db/db mice than these in the control ones were observed. Dynamic pacing showed increased incidence of spatially discordant alternans leading to more VA inducibility in the db/db mice. Western blot analyses revealed increased phosphorylated-Ca2+ /calmodulin-dependent protein kinase II protein expression and decreased ryanodine receptor protein expression, which probably underlay the molecular mechanisms of enhanced arrhythmogenicity in db/db mice.

Conclusions: The type 2 diabetic mouse hearts show impaired repolarization, Cai handling homeostasis, and cardiac conduction reserve, leading to vulnerability of spatially discordant alternans development and induction of VA. Altered Cai -handling protein expressions probably underlie the molecular mechanisms of arrhythmogenicity in the type 2 diabetes animal model.

Keywords: arrhythmia; conduction velocity; db/db mouse; intracellular calcium dynamics; type 2 diabetes.

PubMed Disclaimer

LinkOut - more resources